%0 Journal Article
%A Szibor, Marten
%A Gizatullina, Zemfira
%A Gainutdinov, Timur
%A Endres, Thomas
%A Debska-Vielhaber, Grazyna
%A Kunz, Matthias
%A Karavasili, Niki
%A Hallmann, Kerstin
%A Schreiber, Frank
%A Bamberger, Alexandra
%A Schwarzer, Michael
%A Doenst, Torsten
%A Heinze, Hans-Jochen
%A Lessmann, Volkmar
%A Vielhaber, Stefan
%A Kunz, Wolfram S.
%A Gellerich, Frank N.
%T Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply
%J The journal of biological chemistry
%V 295
%N 14
%@ 0021-9258
%C Bethesda, MD.
%I American Soc. for Biochemistry and Molecular Biology8772
%M DZNE-2020-01050
%P 4383-4397
%D 2020
%X Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca2+). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that adaptive activation of mitochondrial dehydrogenases by intramitochondrial Ca2+ cannot be the exclusive mechanism for OXPHOS control. We hypothesized that cytosolic Ca2+, but not mitochondrial matrix Ca2+, may adapt OXPHOS to workload by adjusting the rate of pyruvate supply from the cytosol to the mitochondria. Here, we studied the role of malate-aspartate shuttle (MAS)-dependent substrate supply in OXPHOS responses to changing Ca2+ concentrations in isolated brain and heart mitochondria, synaptosomes, fibroblasts, and thymocytes from WT and MCU KO mice and the isolated working rat heart. Our results indicate that extramitochondrial Ca2+ controls up to 85
%K Animals
%K Aspartic Acid: metabolism
%K Brain: metabolism
%K Calcium: metabolism
%K Calcium Channels: deficiency
%K Calcium Channels: genetics
%K Cytosol: metabolism
%K Glutamic Acid: chemistry
%K Glutamic Acid: metabolism
%K Heart: physiology
%K Malates: chemistry
%K Malates: metabolism
%K Membrane Potential, Mitochondrial
%K Mice
%K Mice, Inbred C57BL
%K Mice, Knockout
%K Mitochondria: metabolism
%K Myocardium: metabolism
%K Oxidative Phosphorylation
%K Pyruvic Acid: metabolism
%K Rats
%K Substrate Specificity
%K Synaptosomes: metabolism
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC7135991
%$ pmid:32094224
%R 10.1074/jbc.RA119.011902
%U https://pub.dzne.de/record/151065